Pharmacokinetic Calculations Research Articles

Pharmacokinetics and endometrial and tubal tissue penetration of cefalotin and cefazolin

The pharmacokinetics and concentrations of the two antibiotics cefazolin and cefalotin were studied during gynecologic operations in endometrial and tubal tissue. The patients received 0.05 g/kg of the antibiotics by intravenous injection. Under the given conditions, pharmacokinetic calculation of the plasma elimination gave half-lives of 24.8 min for cefalotin and of 63 min for cefazolin. Fitting of the tissue levels to the Bateman function showed that the two antibiotics diffuse rapidly into both tubal and endometrial tissue and attain peak concentration levels between 10 and 25 min. In both tissues the concentrations of cefazolin were higher than those of cefalotin. Higher tissue concentrations of cefazolin could also be demonstrated in experiments of longer duration.

Report of a Case of: Suspected Digoxin Malabsorption

A case involving suspected digoxin malabsorption is presented. Two clinical tests of malabsorption, D-xylose and serum carotene are explained. Several pharmacokinetic calculations are made to theoretically predict the patient's serum digoxin concentration. Other data is presented to compare with the patient's response. The significance of altered renal function and bioavailability of digoxin are discussed and the relationship between hyperthyroidism and serum digoxin determinations is mentioned. Several alternative therapies for use in cases of malabsorption are discussed.

Pharmacokinetic analysis of blood level data interpreted by a two-compartment model.

Although a two-compartment model represents an adequate model for a reasonably sophisticated description of the time course of many drugs in the body, the still simpler one-compartment model provides certain pharmacokinetic parameters which are useful, particularly in clinical application. A single-compartment approximation may be made under certain conditions by omitting blood level data in the period shortly after rapid intravenous administration. Pharmacokinetic calculations utilizing the parameters from this approximation were compared with those based on the true two-compartment model. Simple equations were developed to test the validity of the single-compartment approximation. Errors in the calculated values based on the single-compartment approximation were expressed in terms of the smaller exponent β and ratios (m=A/B and n-α/β) of the coefficients and the exponents from biexponential fitting to blood level data after rapid intravenous administration. It was shown that the single-compartment approximation may or may not be satisfactorily used for clinical purposes depending upon size of m and n or relative size of m and n. Using the formulas derived in this report and data from intravenous administration on a few patients, it is possible to determine for a particular drug whether the one-compartment model is an adequately approximate model for clinical purposes, or whether the two-compartment model is really necessary.

Influence of Formulating Factors on Drug Safety of Timed-Release Nitroglycerin Tablets

A peroral sandwich model tablet with timed release, containing proxyphylline and nitroglycerin, was developed. One layer of the tablet constituted the rapidly disintegrating and dissolving initial phase; the other, the depot phase, was in the form of an insoluble, indigestible skeleton. Amount of drugs in the tablet and their liberation rate constants were based on pharmacokinetic calculations. Upon chewing and masticating a depot tablet, the retard action usually is lost due to an increase of the surface. This problem would not be serious with proxyphylline, which is relatively nontoxic, but could be dangerous or fatal in the case of nitroglycerin. To obtain safety with this product, proxyphylline of the depot phase was incorporated into the pores of an indigestible plastic skeleton of the matrix, and nitroglycerin was dissolved in the plastic particles of the matrix. In vitro and in vivo experiments proved the loss of depot action for both drugs upon mastication of the tablet, yet the nitroglycerin release was slow enough not to cause unwanted side effects.